Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment

Abstract

Background: Identification of modifiable risk factors that affect cognitive decline is important for the development of preventive and treatment strategies. Status of paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme, may play a role in the development of neurological diseases, including Alzheimer’s disease. Objective: We tested a hypothesis that PON1 status predicts cognition in individuals with mild cognitive impairment (MCI). Methods: Individuals with MCI (n = 196, 76.8-years-old, 60% women) participating in a randomized, double-blind placebo-controlled trial (VITACOG) were assigned to receive a daily dose of folic acid (0.8 mg), vitamin B12 (0.5 mg) and B6 (20 mg) (n = 95) or placebo (n = 101) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of participants (n = 168) by MRI. PON1 status, including PON1 Q192R genotype, was determined by quantifying enzymatic activity of PON1 using paraoxon and phenyl acetate as substrates. Results: In the placebo group, baseline phenylacetate hydrolase (PhAcase) activity of PON1 (but not paraoxonase activity or PON1 Q192R genotype) was significantly associated with global cognition (Mini-Mental State Examination, MMSE; Telephone Inventory for Cognitive Status-modified, TICS-m), verbal episodic memory (Hopkins Verbal Learning Test-revised: Total Recall, HVLT-TR; Delayed Recall, HVLT-DR), and attention/processing speed (Trail Making A and Symbol Digits Modalities Test, SDMT) at the end of study. In addition to PhAcase, baseline iron and triglycerides predicted MMSE, baseline fatty acids predicted SDMT, baseline anti-N-Hcy-protein autoantibodies predicted TICS-m, SDMT, Trail Making A, while BDNF V66M genotype predicted HVLT-TR and HVLT-DR scores at the end of study. B-vitamins abrogated associations of PON1 and other variables with cognition. Conclusion: PON1 is a new factor associated with impaired cognition that can be ameliorated by B-vitamins in individuals with MCI.

B Vitamins Prevent Iron-Associated Brain Atrophy and Domain-Specific Effects of Iron, Copper, Aluminum, and Silicon on Cognition in Mild Cognitive Impairment

“…In multiple regression analysis for the placebo group, global cognition at the end of study (MMSE_2) was determined by baseline Fe_1, Al_1, and tHcy_1 as well as brain atrophy rate and baseline MMSE_1 score; adjusted R 2 was 0.50 (Model 1, Table 3 ). PhAcase_1 and triglycerides (TG_1), identified in the previous study as contributing to the variance [ 29 ], were also included in the analyses ( Table 3 ). Cys_1 and age, significantly associated with MMSE_2 in bivariate analysis, was not significant in multiple regression analysis.…”

The Relationship Between Mild Cognitive Impairment and Anti-Inflammatory/Pro-Inflammatory Nutrients in the Elderly in Northern China: A Bayesian Kernel Machine Regression Approach

“…The neuroinflammation can lead to some problems related to the pathophysiology of mild cognitive impairment, including hypothalamic-pituitary-adrenal axis disorders, reduced neuroplasticity and neurogenesis; 36 , 37 increased glutamate, which boosted neurotoxicity; varied monoamine metabolism and decreased serotonin additionally increases the quinine pathway; reduces brain-derived neurotrophic issue (BDNF); increases oxidative stress, amongst which inflammatory oxidative stress plays a vital role. 38 , 39 …”

“…In addition, the body needs enough vitamin B to maintain the homeostasis. 51 B6, folic acid (B9) and B12 metabolize homocysteine (Hcy), which is a non-protein, sulfur-containing amino acid produced during single-carbon metabolism. Studies have shown that Hcy is a biomarker of inflammation, and as the level of Hcy increases, the risk of cardiovascular disease and neurological disease increases significantly.…”

Mechanistic Link between Vitamin B12 and Alzheimer’s Disease

“…In the intervention group, B vitamins ameliorate the detrimental effects of PON1 on cognition. This study highlighted a novel positive aspect of B vitamin treatment on the central nervous system [ 164 ]. In contrast, a randomized controlled trial from 2010, investigating the effect of supplementation with daily doses of 2 mg folic acid, 25 mg vitamin B6 and 500 µg vitamin B12 over two years, did not detect any beneficial effects of B vitamins on cognitive function or the risk of cognitive impairment or dementia.…”